An international team of scientists — some of whom succumbed to the virus during the course of their research — has sequenced 99 Ebola virus genomes from 78 patients in Sierra Leone, creating a valuable trove of genetic data for scientists and health care workers struggling to bring the growing outbreak under control.

The study increased the amount of genomic data available on the Ebola virus by four-fold, according to a press release.

According to the World Health Organization, the Ebola outbreak in West Africa eventually could exceed 20,000 cases, more than six times as many as are now known, and vastly higher than the largest outbreak-to-date, which included about 400 cases.

The study, published Thursday in the journal Science Express, provides clues to the origin of the outbreak in Sierra Leone, in much the same way as police detectives use fingerprints at a crime scene to track down a suspect. The data points to the introduction into Sierra Leone of two genetically distinct lineages of the Ebola virus, officially known as EBOV, from Guinea at about the same time, traced to a dozen individuals who attended the same funeral of an Ebola patient in Guinea.

Map of Sierra Leone, including the capital city of Kenema.

Image: Stephen Gire

The genetic data shows that the Ebola strains responsible for the current outbreak are distinct, with unique mutations, but that they likely have a common ancestor traced to the first recorded outbreak in 1976.

The ongoing outbreak began in Guinea and spread to Sierra Leone, Liberia and Nigeria. A separate outbreak has also been reported in the Democratic Republic of Congo.

"We were able to sequence and analyze our samples with about a 10-day turnaround. This is unprecedented, as earlier studies have usually taken many months with much smaller datasets," says Daniel J. Park, a co-author and computational biologist at the Broad Institute, in an email interview with Mashable.

The research, which used an advanced genetic analysis technique known as deep sequencing, reveals that the disease is rapidly accumulating mutations as it spreads.

The team found 395 genetic changes, including 341 that make this outbreak distinct from the viral genomes tied to previous Ebola outbreaks, and 50 that are unique to the West African outbreak more broadly.

Of particular interest are mutations that alter protein sequences, since they could potentially change the accuracy of diagnostic tests for the virus as well as vaccines and therapies. It is unclear if these mutations are related to the severity of the current outbreak, but further genetic analysis could determine this.

Illustration of the Congo River to show it bending in a shape similar to the Ebola virus under a microscope.

Image: Stephen Gire

"What we know is that as the virus continues to change during an outbreak. As a result, it might stumble upon evolutionary opportunities that it hasn’t experienced before," Park said. "The longer the outbreak continues, the more opportunities the virus has. Whether this will lead to changes that affect disease transmission or progression, we are unable to say."

Deep sequencing means that researchers read the Ebola virus genome "to a very high level of accuracy and depth," Park said. "The EBOV genome (like many other viral genomes) consists of a strand of RNA composed of individual nucleotides (called bases). When we sequence to such a high median coverage, it means the average base in the genome is read over 2000 times."

Park says that this technique "is extremely accurate" since it allows researchers to sequence every single base multiple times, leading to a higher detection rate of mutations that would go unnoticed by conventional sequencing techniques.

"We can see how the virus changes within an individual. Each infected patient has a very large number of viral particles, and some of these might be slightly different," he said. "Using ‘deep sequencing’ we are able to see these differences and therefore get a much better picture of the viral population within an individual host."

The late Dr. Sheik Humarr Khan, who passed away from the Ebola virus before the study was published.

Image: Pardis C. Sabeti

The new genetic data, which were made freely available in June for researchers online at the National Center for Biotechnology Information's (NCBI's) DNA sequence database, also allowed scientists to trace the disease's entry into Sierra Leone and subsequent spread. According to the study, the Ebola virus disease that is affecting Sierra Leone likely spread from Central Africa about a decade ago. It says the three most recent outbreaks are independent events in which the virus spread from its natural reservoir, which is thought to be fruit bats, to humans.

"It’s impossible to know for sure how the virus traveled from locations where it’s ancestral variants were located in Central Africa," Park says.

Scientists are still struggling to identify the disease reservoir and determine how many different genetic variants of the virus are circulating within it. "The only way to really unravel this story would be to sequence the reservoir for Ebola, which is currently thought to be bats," Park says. "This deserves deeper investigation, but this may be very difficult technically, as most bats will not carry the virus at a given moment in time. This means that a large number of bats (perhaps thousands) would have to be captured, samples taken, and sequencing performed — all under safe conditions.

"Our hope is that this effort establishes a precedent for how sequencing can be used in emergency response efforts for an outbreak. Sequencing the pathogen should be an integral part of outbreak response, as it can be very practical in providing insights into disease control, epidemiology, diagnostics, and treatments," Park told Mashable.

With sequencing, medical professionals and researchers could, in theory, more quickly identify a pathogen's original source, changes it's undergoing as it spreads, and deploy changed testing and treatment protocols to take into account any mutations.

"Sequencing can now be produced very quickly and cheaply, and with negligible disruption in the field. These efforts help to develop scientific and laboratory capabilities on the ground, making for a far more rapid and effective response to epidemics," Park said.

Illustration of blood cells.

Image: Stephen Gire

The study was the result of a collaboration between the Broad Institute and Harvard University, as well as European universities and the Sierra Leone Ministry of Health and Sanitation.

The five researchers who died of Ebola virus disease before the paper was published were all Sierra Leonean collaborators. According to Park, many of these researchers had family members who contracted the disease, while others were infected while caring for patients.

Among the deceased researchers were senior disease experts, such as Sheik Humarr Khan, who was the director of the National Lassa Fever Program for the Ministry of Health and Sanitation in Sierra Leone. Lassa Fever is another dangerous viral hemorrhagic fever that affects parts of Africa. In addition, Mbalu Fonnie was a senior matron of nursing at the Kenema Government Hospital who specialized in treating Lassa cases in pregnant women.

"There is an extraordinary battle still ahead, and we have lost many friends and colleagues already like our good friend and colleague Dr. Humarr Khan, a co-senior author here," said study co-author Pardis Sabeti of the Broad Institute. "By providing this data to the research community immediately and demonstrating that transparency and partnership is one way we hope to honor Humarr's legacy. We are all in this fight together."

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